DESCRIPTION: The eye relies on the aqueous humor for nutrition of the cornea, lens, vitreous and trabecular meshwork, as well as the removal of the waste products of metabolism from these tissues. Steady formation and discharge of the aqueous maintains the intraocular pressure and the optical shape of the eye. A number of drugs commonly used in the treatment of glaucoma lower the intraocular pressure by suppressing the rate of aqueous formation. The ciliary body epithelium is responsible for the formation of aqueous humor and is the target of these drugs. The objective of this project is to characterize in detail the pharmacology and physiology of drug-induced responses and increases in second messengers activity in this epithelium. The PI is particularly interested in the role of Ca2+. The previous studies on intact ciliary body epithelium and on dissociated epithelial cells have shown that many neurotransmitters and hormones act on the cells of ciliary body by increasing the intracellular free Ca2+ concentration. He will use fluorescence ratio imaging on intact as well as dissociated cells to investigate the pharmacology and physiology of the Ca2+ rise in some detail. He will use intracellular recording on intact tissue and patch-clamp recording on dissociated cells to identify influx pathways for Ca2+,as well as other conductive pathways involved in intracellular Ca2+ increase. He will then attempt to identify and characterize the ion channels and transporters modulated by the Ca2+ rise. The PI hope is that he can identify mechanisms involved in the modulation of intracellular Ca2+ concentration and aqueous formation, which may provide new tools for clinical intervention.